The effect of iron fortification of complementary foods on infant gut microbiota

描述（由申请人提供）：婴儿和2岁以下的儿童是缺铁性贫血发病率最高的年龄组。向这个年龄组提供足够的膳食铁是一个挑战，使用微量营养素粉在家庭补充食物中进行铁强化是一种有前途的方法。然而，世卫组织建议，在疟疾地区，在证明其安全性之前，不要无针对性地使用含有铁RDA的家庭微量营养素粉。美国国立卫生研究院技术工作组（2009年）“在疟疾负担地区安全有效地使用铁干预措施的考虑因素”的研究重点包括：i）通过不同方式和制剂提供的铁对肠道微生物群落的影响; ii）肠腔中铁促进具有致病潜力的肠道微生物生长的程度。因此，我们计划使用补充的体外和体内研究路线，研究家庭强化中提供的铁对婴儿肠道微生物组的影响。重点是沙门氏菌，作为严重疟疾菌血症研究中最常涉及的病原体。研究的目的是：i）在体内，确定在肯尼亚婴儿中使用含铁微量营养素粉末进行家庭强化是否会改变肠道微生物群的组成和代谢活性，以促进细菌性肠道病原体的生长，并确定特定的 出现的肠道病原体; ii）在体外，在用体内研究中鉴定的特定病原体接种的连续结肠发酵模型中使用固定化的婴儿粪便微生物群落，以及细胞培养沙门氏菌感染模型，以确定结肠铁选择细菌性肠道病原体的机制，包括铁剂量、铁形式以及肠道微生物群对铁的分子和代谢反应。为了彻底表征铁强化对肠道微生物群的全球影响，特别是对肠道病原体的影响，我们将应用TTGE，POR，高通量16 S rRNA基因序列分析，HPLC法SCFA生产以及宏基因组学方法来测量基因型效应。 公共卫生相关性：该项目应提供有关膳食铁和婴儿肠道微生物群之间相互作用的基本知识，以便设计安全有效的家庭强化策略，以控制传染病负担高的热带国家婴儿的缺铁性贫血。

DESCRIPTION (provided by applicant): Infants and children < 2 yrs are the age group with the highest rates of iron deficiency anemia. Provision of sufficient dietary iron to this age group is a challenge, and in-home iron fortification of complementary foods using micronutrient powders is a promising approach. However, WHO has recommended against untargeted use of in-home micronutrient powders that contain the iron RDA for a child in a single dose in malarial areas, until their safety is proven. Research priorities from the U.S. NIH Technical Working Group (2009) "Considerations for the safe and effective use of iron interventions in areas of malaria burden" include: i) effect of iron delivered through different means and formulations on gut microflora; ii) extent to which iron in the gut lumen favors growth of enteric microorganisms with a pathogenic potential. Therefore, we plan to investigate the effect of iron provided in in-home fortification on the infant gut microbiome, using complementary in vitro and in vivo lines of investigation. The focus is on Salmonella spp., as the pathogen most often implicated in studies of bacteremia in severe malaria. The study aims are: i) in vivo, to determine if in-home fortification using an iron-containing micronutrient powder in Kenyan infants at high risk for diarrheal disease and malaria will modify the composition and metabolic activity of the gut microbiota to favor growth of bacterial enteropathogens, and identify the specific enteropathogens that emerge; ii) in vitro, using immobilized infant fecal microflora in a continuous colonic fermentation model inoculated with the specific pathogens identified in the in vivo studies, as well as a cell culture Salmonella infection model, to determine the mechanisms by which colonic iron selects for bacterial enteropathogens, including iron dose, iron form and the molecular and metabolic response of the gut microbiota to iron. To thoroughly characterize the global impact of iron fortification on the gut microbiota and specifically, on enteropathogens, we will apply TTGE, POR, high-throughput 16S rRNA gene sequence analysis, SCFA production by HPLC as well as metagenomic approaches to measure genotype effects. PUBLIC HEALTH RELEVANCE: This project should provide basic knowledge on the interactions between dietary iron and the infant gut microbiota in order to design safe and effective in-home fortification strategies to control iron deficiency anemia in infants in tropical countries with high burdens of infectious disease.